1. Field of the Invention
The present invention relates to diagnosis and therapeutics of tumors of animal including human as well as a radioactive diagnostic and radioactive therapeutic agent useful for such purpose.
2. Background Arts
Pharmaceuticals in which a substance accumulating in tumor is bound to a radionuclide have been developed in order to diagnose tumor grown in body of animal including human.
Because of harmfulness of the radionuclides against cells, it is desirable that the pharmaceuticals do not accumulate in the normal region but are bound only to tumor cells, accumulating therein for a long period.
While therapeutics including systemic chemotherapy, intraperitoneal chemotherapy, beam radiotherapy, intracavitary radioactive colloid instillation and so on were attempted by Lacy et al. for therapeutics of intraperitoneal tumor (Lacy et al, Management of Malignant Ascites, Surg. Gynecol. Obstet., 159, 397-412, 1984), no approach has demonstrated sufficient efficacy.
Targeting therapeutics using anti-tumor monoclonal antibodies conjugated with radionuclides, chemotherapeutics or toxins could be highly specific to tumors, less toxic to normal cells and highly toxic to tumors. Particularly, attempts for therapeutics of intraperitoneal tumor with radiolabeled antibodies were found effective for animal patients including human. However, the administration of radioactive species for therapeutic purpose was limited because the blood radioactivity level and nonspecific uptake of radiolabeled substance into normal tissues were undesirably high.
It has been described by Lotan (R. Lotan, Lectins in Cancer Cells, Annals of New York Academy of Sciences, 551, 385-398, 1988) that lectins are present on the surface of tumor cell and that ligands bound to lectins are internalized by the cells. Lectins are proteins bound to saccharides, have two or more binding sites, agglutinate animal and plant cells, and precipitate polysaccharides and complex carbohydrates. Their binding specificity can be defined by inhibition test using monosacchrides and oligosaccharides, and various lectins have been known. It can be said that substances specifically recognizing lectins on a tumor surface are promising for tumor controlling but no effective substance has been reported showing sufficiently high uptake for allowing image processing.
In view of circumstances that no appropriate ligand has been found out in spite of expectation that ligands which can bind to lectins on a surface of tumor cells and can be internalized by the tumor cells from the tumor surface can be carriers useful in diagnosis and therapy of tumors, an object of the present invention is to find out ligands showing sufficiently high accumulation by binding to lectins and to provide radioactive diagnostic and therapeutic agents useful in diagnosis and therapeutics of tumors by binding radionuclides to said ligands.
In order to solve such problem, the present inventors have conducted extensive studies and have found out, as a result, glycoproteins having molecules capable of binding to lectins on a tumor surface, and successfully completed the present invention.